2. Academic Validation
  3. Synergistic effects of the curcumin analog HO-3867 and olaparib in transforming fallopian tube epithelial cells

Synergistic effects of the curcumin analog HO-3867 and olaparib in transforming fallopian tube epithelial cells

  • Invest New Drugs. 2025 Aug 4. doi: 10.1007/s10637-025-01571-2.
Cai-Chieh Tseng 1,  Min-Hsi Ku 1,  Wei-Min Wu 2,  Ava Mendez 3,  Tessa Christner 3,  Yun-Chieh Wu 1,  Wei-Lun Huang 1,  Yu-Hsiang Chen 1,  Ching-Wen Huang 1,  Johnathan Barefoot 3,  Chi-Wei Chen 4 5
Affiliations

Affiliations

  • 1 Department of Biochemical and Molecular Medical Sciences, College of Science and Engineering, National Dong Hwa University, Hualien, 974301, Taiwan, R.O.C.
  • 2 Department of Natural Resources and Environmental Studies, College of Environmental Studies, National Dong Hwa University, Hualien, 974301, Taiwan, R.O.C.
  • 3 Department of Biology, College of Arts and Sciences, Appalachian State University, Boone, NC, 28608, USA.
  • 4 Department of Biochemical and Molecular Medical Sciences, College of Science and Engineering, National Dong Hwa University, Hualien, 974301, Taiwan, R.O.C.. chenc4@appstate.edu.
  • 5 Department of Biology, College of Arts and Sciences, Appalachian State University, Boone, NC, 28608, USA. chenc4@appstate.edu.
PMID: 40760233 DOI: 10.1007/s10637-025-01571-2
Abstract

Ovarian Cancer remains one of the most lethal gynecologic malignancies, largely due to high recurrence rates and treatment-related toxicities. Although PARP inhibitors like Olaparib have shown efficacy in BRCA-mutated cancers, their benefit is limited in broader patient populations. TP53 mutations, highly prevalent in ovarian Cancer, promote tumor progression and resistance, making p53 a key therapeutic target. This study evaluated the Anticancer potential of HO-3867, a curcumin analog known to restore mutant p53 function, alone and in combination with Olaparib. We used fallopian tube-derived ovarian Cancer models harboring mutant or null TP53 and analyzed TP53 expression and mutation profiles using TCGA datasets. Molecular docking simulations and cellular thermal shift assays (CETSA) confirmed HO-3867 binding to the p53Y220C mutant core domain. Cytotoxicity was assessed via SRB assays; flow cytometry and Western blotting were used to examine cell cycle progression, Apoptosis, and DNA damage. HO-3867 treatment increased phospho-p53 (Ser15) and p21 expression, induced G1 phase arrest, and suppressed cell viability. Notably, co-treatment with Olaparib synergistically enhanced Apoptosis, as indicated by increased Caspase-3 and PARP1 cleavage and elevated γH2AX levels. These findings suggest that HO-3867 reactivates mutant p53 and potentiates Olaparib efficacy by promoting Apoptosis and amplifying DNA damage, offering a promising therapeutic strategy for TP53-mutant ovarian Cancer.

Keywords

TP53; Curcumin analog; HO-3867; Ovarian cancer; PARP inhibitor; Transforming fallopian tube epithelial cells.

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